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Activity in dorsal anterior cingulate cortex (dACC) dynamically tracks the value of the choice after every outcome. Here the authors report that dACC represents topographic maps of value estimates for different learning rates and interacts with similar maps in other areas at the time of the decision.

A model of compositional state spaces in the hippocampus shows latent learning and rapid generalization. Bakermans et al. show that this model predicts the emergence of place responses in replay.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

Samborska et al. trained mice on a set of problems with the same structure but different physical layouts to study generalization. Neurons in prefrontal cortex generalized across problems, whereas those in hippocampus were more problem specific.

Mice generalize complex task structures by using neurons in the medial frontal cortex that encode progress to task goals and embed behavioural sequences.

Muller et al. show that some neurons in the cortex learn faster from better-than-expected outcomes compared to worse-than-expected ones; others do the converse, resulting in simultaneous optimism and pessimism, as predicted by distributional reinforcement learning.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Lindsey Criswell and colleagues report an association between three independent variants near TNFAIP3 and systemic lupus erythematosus (SLE). In a related study, Patrick Gaffney and colleagues report results of a genome-wide association study for SLE, also identifying variants in the TNFAIP3 region on 6q23 that are strongly associated with the disease. The same region on 6q23 has recently been associated with rheumatoid arthritis, but only a subset of risk alleles in this region seem to be common to both diseases.

The role of dopamine in foraging behaviour in humans is not well understood. Here, the authors show using PET imaging, that striatal dopamine receptor availability, and dopamine function in the anterior cingulate cortex and mesolimbic areas are related to the decision to explore new environments.

Huntington disease (HD) has been linked via biochemical uptake assays to impaired glutamate clearance and resultant excitotoxicity. Here, utilizing a fluorescent reporter, the authors measure real-time glutamate dynamics in mouse model HD brain slices and find normal or even accelerated glutamate clearance.

This study uses simultaneous EEG-fMRI to investigate how the brain replays past experiences, revealing that transient replay events by EEG correspond with increased hippocampal activity and enhanced connectivity with the default mode network in fMRI.

Coxsackievirus A6 (CVA6) causes hand, foot and mouth disease in children. Here the authors present the CVA6 procapsid and A-particle cryo-EM structures and identify an immune-dominant neutralizing epitope, which can be exploited for vaccine development.

Hunt, Malalasekera et al. recorded populations of prefrontal neurons from monkeys performing a visual attention-guided-choice task. The results revealed that distinct computations in three PFC subregions as information was sampled guided the eventual decision.

Lennart Hammarström, Tim Behrens and colleagues report the results of a genome wide association study of selective immunoglobulin A deficiency, the most common form of primary immunodeficiency in humans. They validated previously known HLA haplotype associations and identified a new risk variant in IFIH1.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Patrick Gaffney and colleagues report results of a genome-wide association study for systemic lupus erythematosus (SLE), identifying variants in the TNFAIP3 region on 6q23 that are strongly associated with the disease. In a related study, Lindsey Criswell and colleagues report a similar association between variants near TNFAIP3 and SLE. The same region on 6q23 has recently been associated with rheumatoid arthritis, but only a subset of risk alleles in this region seem to be common to both diseases.

Hahamy et al. demonstrate that, at the transitions between narrative events, the human brain reactivates past information that is relevant for the understanding of the current narrative stage.

Brain regions exhibit specialization for different functions, but such functions are constrained by anatomical connections to other brain regions. A study now finds that, by measuring these connections, we can predict complex functional responses before the subject has even performed the task.

Wimmer et al. show that successful recall of an extended episode of experience in humans is associated with temporally compressed replay of neural patterns associated with the memory, and that the direction of replay depends on task goals.

Humans are able to exploit patterns or schemas when performing new tasks, but the mechanism for this ability is still unknown. Using graph-learning tasks, we show that humans are able to transfer abstract structural knowledge and suggest a computational mechanism by which such transfer can occur.

Although previous work has shown that extensive training in the complex visuo-motor skills involved in juggling results in adult gray-matter changes, it is unclear whether such practice can produce similar changes in adult white matter. This paper now uses diffusion tensor imaging to demonstrate structural white-matter changes when adults practice juggling.

B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.

This study uses a combination of computational modeling and magnetoencephalography to track activity while people make decisions, and finds that prefrontal and parietal cortex activity is consistent with mutual inhibition between competing options during decision-making. This activity is likely to represent a mechanism for the comparison of values while making choices.

Here the authors show that ventromedial prefrontal cortex (vmPFC) levels of GABA and glutamate in human volunteers are predictive of both behavioral performance and the dynamics of a neural value comparison signal in a manner as predicted by models of decision-making, thus providing evidence for neural competition in vmPFC supporting value-guided choice.

Timothy Vyse and colleagues report the results of a large-scale association study of systemic lupus erythematosus (SLE). They identify ten new susceptibility loci and implicate aberrant regulation of innate and adaptive immunity genes in disease pathogenesis.

A coding mutation in APP, the gene that encodes the amyloid-β precursor protein, is found to protect against Alzheimer’s disease and cognitive decline in the elderly without Alzheimer’s disease.

This study used fMRI repetition suppression to demonstrate that human subjects can represent and evaluate novel choice options by invoking multiple memories for previous experiences in hippocampus and medial prefrontal cortex.

Robert Graham and colleagues report results of a large-scale replication study for systemic lupus erythematosus (SLE) in individuals of European ancestry. Their findings expand the number of confirmed SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

The authors use computational modeling of participants' performance on an aversive learning task to examine how decision-making is altered in anxiety. Results indicate that anxious individuals struggle to use information regarding the stability of action-outcome relationships to guide their choices. Pupillometry data link this deficit to altered norepinephrinergic function.

Evans, Blake, Longworth and colleagues identify and characterize a tumour-suppressive role for microglia that mediate a pro-inflammatory response to restrict brain metastasis in breast cancer.

Detecting tumor recurrences early and developing therapies capable of targeting recurrences that resist frontline therapy could be of enormous benefit to patients with cancer. Using mouse tumor models, Richard Vile and colleagues find a cytokine signature associated with very early stage recurrences, as well as evidence that the recurrent tumors are resistant to innate immune responses. By targeting the altered phenotype of the recurrent tumors, the researchers cured the mice of cancer, suggesting new avenues for research into human cancer recurrence.

This study uses a combination of human fMRI and computational modeling to show that decision-making can be explained by a hierarchical model involving competition between different options at many different levels of representation. These results do not support a model where competition happens only at a final choice stage.

Peter Gregersen and colleagues identify a regulatory variant in CSK, coding for an intracellular kinase that physically interacts with Lyp (PTPN22), associated with systemic lupus erythematosus (SLE). Their work suggests that the Lyp-Csk complex influences susceptibility to SLE through regulation of B-cell signaling, maturation and activation.

This study reports a double dissociation in the neuronal correlates of value-based decision making in monkey prefrontal cortex, with orbitofrontal cortex neurons encoding choice value relative to recent choice values, while anterior cingulate cortex neurons flexibly encode multiple decision parameters and reward prediction errors using a 'common valuation currency'.

PIKfyve is a lipid kinase essential for regulation of membrane homeostasis and vesicle trafficking along the endosomal-lysosomal pathway. Here the authors show that mice lacking PIKfyve exclusively in their platelets exhibit a systemic disorder characterized by multi-organ inflammation and thrombosis due to aberrant platelet lysosome function.

Large-scale, multimodal phenotypic characterisation is a valuable tool to explore brain function. Poldrack et al. collect and relate MRI, psychological, physiological, metabolic and gene expression data from a single human over an 18 month period, providing a rich resource for future studies.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.

This paper describes an integrated approach for neuroimaging data acquisition, analysis and sharing. Building on methodological advances from the Human Connectome Project (HCP) and elsewhere, the HCP-style paradigm applies to new and existing data sets that meet core requirements and may accelerate progress in understanding the brain in health and disease.